Treatment of acute lung injury by inhibition of gene induction of NO synthase in alveolar macrophages.

通过抑制肺泡巨噬细胞中 NO 合酶的基因诱导来治疗急性肺损伤。

• 批准号: 12670579
• 负责人: TAMAOKI Jun
• 金额: $ 2.56万
• 依托单位: Tokyo Woman's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670579/
• 关键词: Macrophage; Nitric Oxide; Gene therapy; Lung injury; Cytokines; Macrolide; Erythromycin; Clarithromycin; 遺伝子治療; 急性肺傷害; クラリスロマイシン; ポーラログラフィー

Macrolide antibiotics have unique immunomodulatory actions apart from antimicrobial properties. We studied the effects of macrolides on immunoglobulin G immune complex (IgG-ICx)-induced lung injury in rats in vivo and in vitro. Intrapulmonary deposition of IgG-ICx produced a time-dependent increase in the concentration of NO in exhaled air. There were corresponding increases in the number of neutrophils accumulated into alveolar spaces, and lung wet-to-dry weight ratio. All of these changes were inhibited by pretreatment with erythromycin or josamycin, but not by amoxicillin or cephaclor. Incubation of cultured pulmonary alveolar macrophages (PAM) caused upregulation of NO production and expression of inducible NO synthase (iNOS) mRNA, an effect that was dose dependently inhibited by erythromycin, roxithromycin, or josamycin. The macrolides also reduced IgG-ICx-induced release of IL-1* and TNF-α, but did not alter the release of NO induced by exogenously added IL-1β and TNF-α. These results suggest that macrolide antibiotics specifically inhibit immune complex-induced lung injury presumably by inhibiting cytokine release and the resultant downregulation of iNOS gene expression and NO production by rat PAM.

除抗菌特性外，大环内酯类抗生素还具有独特的免疫调节作用，我们在体内和体外研究了大环内酯类药物对免疫球蛋白 G 免疫复合物 (IgG-ICx) 诱导的肺损伤的影响。呼出空气中一氧化氮浓度增加，肺泡腔中积聚的中性粒细胞数量以及肺湿干重比也相应增加。红霉素或交沙霉素预处理可抑制培养的肺泡巨噬细胞 (PAM)，但不会被阿莫西林或头孢克洛抑制。 、罗红霉素或交沙霉素也可减少 IgG-ICx 诱导的 IL-1* 释放。和 TNF-α，但不改变外源添加的 IL-1β 和 TNF-α 诱导的 NO 释放。这些结果表明，大环内酯类抗生素可能通过抑制细胞因子释放和由此导致的 iNOS 下调来特异性抑制免疫复合物诱导的肺损伤。大鼠 PAM 的基因表达和 NO 产生。

项目成果

玉置淳: "呼吸器疾患とマクロライド療法"分子呼吸器病. 4. 413-418 (2000)

Jun Tamaki：“呼吸系统疾病和大环内酯治疗”《分子呼吸系统疾病》4. 413-418 (2000)。

Tamaoki J: "Effects of macrolides on lung injufy induced by lgG immune complex."Jap J Antibiot. 54. 83-86 (2001)

Tamaoki J：“大环内酯类药物对 IgG 免疫复合物诱导的肺损伤的影响。”Jap J Antibiot。

Tamaoki Jun: "Impairment of airway mucociliary transport in patients with sinobronchial syndrome"Journal of Aerosol Medicine. 13. 239-244 (2000)

Tamaoki Jun：“窦支气管综合征患者气道粘液纤毛运输受损”气溶胶医学杂志。

Tamaoki Jun: "Molecular mechanism of airway remodeling in asthma"Recent Research Developments in Clinical Immunology. 4. 1-10 (2001)

玉木俊：《哮喘气道重塑的分子机制》临床免疫学最新研究进展。

玉置 淳: "気管支・肺の防御機構と呼吸器疾患"埼玉県医学会雑誌. 36. 154-158 (2001)

Jun Tamaki：“支气管肺防御机制和呼吸系统疾病”，埼玉县医学会杂志 36. 154-158 (2001)。